Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; methods ; Neoplasms ; diagnosis ; drug therapy ; prevention & control ; Phytotherapy ; Treatment Outcome

Animals ; Apoptosis ; physiology ; Carcinoma, Squamous Cell ; drug therapy ; physiopathology ; prevention & control ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors ; therapeutic use ; Head and Neck Neoplasms ; drug therapy ; physiopathology ; prevention & control ; Humans ; Membrane Proteins ; Neoplasm Invasiveness ; Neoplasm Metastasis ; drug therapy ; Neovascularization, Pathologic ; drug therapy ; metabolism ; Prostaglandin-Endoperoxide Synthases ; metabolism

Objective: To solve the technical bottleneck in the application of membrane technology in pharmaceutical industry and to establish a fast and feasible method for evaluating molecular weight cut-off (MWCO) of ultrafiltration membrane. Methods: Based on works, Panax notoginseng saponins (PNS), R1, Rg1, Rb1, and Rd, were selected as indexes for filtering with series ultrafiltration membranes, the retention rate of PNS was accumulated and analyzed with different MWCOs (1×10³-1 × 10⁵). Results: The relevant equations were fitted by linear and exponential function, the regression coefficients of equations between the retention rates of PNS and MWCOs were bigger than 0.98. Then, the equations were applied for calculating the different MWCOs of being-measured ultrafiltration membranes. Conclusion: Preliminary judgment is obtained by comparison analysis of cumulative retention rate, and then the optimal MWCO under tested membranes is calculated by subsection equations. This research results have provided a simple and rapid method of evaluating the membrane MWCOs for pharmaceutical industries.

Objective: To clarify the effect of solution environment on ultrafiltration separation of Panax notoginseng total saponins (PNS) based on the molecular state. Methods: In the experiment, the transmittance and surface tension were selected as indexes for analyzing the effect of ethanol, inorganic salts, surfactants, and pH on the molecular state of PNS. And then, ethanol, NaCl, and pH were selected as influencing factors to analyze the separation rule of notoginsenoside R1 (R1) and ginsenoside Rb1 (Rb1). Results: The intermolecular interaction force of saponins was weakened by increasing the ethanol concentration; The pH value promoted saponin ionization, increased critical micelle concentration, and increased PNS ultrafiltration transmittance; The salting out effect of inorganic salt reduced the critical micelle concentration and PNS transmittance; The surfactant type was related to the ultrafiltration separation behavior of PNS. Rb1 was more sensitive to the factors than R1 by response surface methodology. Conclusion: The effect of solution environmental factors on the ultrafiltration separation of PNS was clarified by the combination of single factor analysis and response surface methodology. And the saponins can be separated purposefully by dynamically adjusting the molecular state.

Objective: To explore the applicability of nanofiltration separation of salvianolic acid B in organic phase. Methods The rejection rate, mass transfer coefficient, membrane flux, membrane durability and membrane integrity were selected as indexes to evaluate the applicability of nanofiltration for the separation of salvianolic acid B raw material in organic phase from the eluate of macroporous resin. Results The experiment showed that there was a negative relationship between rejection rate and membrane molecular weight cut-off. Meanwhile, the mass transfer coefficient of salvianolic acid B was decreased and the membrane flux was obviously decayed with the increase of ethanol concentration. Through the membrane durability and integrity evaluation, the rejection performance of NFG nanofiltration membrane was stable with the increasing of separation time. Also, the membrane flux decreased first and then increased and maintained stable. At the same time, the charge characteristic of the membrane separation layer was stable, but the effective separation aperture was increased by the combined effects of membrane fouling, additives shedding and so on. Conclusion Based on the comprehensive analysis, NFG nanofiltration membrane could meet the requirements of the separation of low concentration ethanol solution, and had good applicability. The applicability of nanofiltration separation in organic phase was analyzed comprehensively with salvianolic acid B as example, providing theoretical and technical support for nanofiltration separation of phenolic acids in organic phase.

Objective To explore the enhanced separation behavior of ferulic acid in organic solution by nanofiltration. Methods In the experiment, molecular weight cut-off (MWCO) of nanofiltration membrane, ethanol concentration, and solution pH were selected as influencing factors to find the sensitive region of ethanol concentration and pH on the retention rate of ferulic acid with Box-Behnken central composite experiment design. And then, the separation rule of ferulic acid with organic solution was analyzed, the correlation between mass transfer coefficient and concentration of organic solvent was fitted with the changed organic solution by nanofiltration mass transfer mathematical model. Results Experiments indicated that the enhanced separation behavior appeared and the mass transfer coefficient decreased as the ethanol concentration increased from 20% to 40% with MWCO 450 and pH 8.0. Under the same condition, the enhanced separation behavior happened as the solvent was changed into methanol and acetonitrile, and the enhanced effect was positively correlated with the concentration of the three common organic solvents, the effect rule was ethanol ≈ methanol > acetonitrile material. Conclusion The enhanced separation effect of nanofiltration was related to the type and concentration of organic solvent. And taking ferulic acid as an example, the mechanism of nanofiltration separation in the environment of organic solution was studied, and the results provided references for nanofiltration concentrate for heat-sensitive traditional Chinese medicine of phenolic acid in organic solution.

Objective To explore the correlation of molecular state of caffeic acid from Perilla frutescens and its nanofiltration mass transfer process. Methods The pH value of solution was changed and the free-dissociation ratio was adjusted with caffeic acid as an index, the rejection and membrane flux of the corresponding initial concentration and operating pressure in different existence conditions were collected. Based on the solution-diffusion effect and charge effect in nanofiltration separation, the linear equations between the rejection and mass transfer coefficient was constructed, the correlation between mass transfer coefficient and initial concentration was established, the mathematical models which based on the operating pressure and initial concentration to predict the rejection of caffeic acid was developed and used to verify its applicability by aqueous extract of P. frutescens. Results Experiments indicated that there was a linear relationship between operation pressure and membrane flux. Besides, mass transfer coefficient and initial concentration of caffeic acid were positively correlated with each other by solution-diffusion effect and charge effect. The mass transfer coefficient of dissociated caffeic acid was less than those of free state and free-dissociation. Moreover, on the basis of power function relationship between mass transfer coefficient and initial concentration, the results showed that the predicted rejections of caffeic acid from P. frutescens water extract using mathematical model approximate well to real ones. Conclusion The mass transfer coefficient of caffeic acid is associated with existential state and initial concentration. The predicted model of nanofiltration separation has a preferable applicability to caffeic acid and provides references for nanofiltration separation, especially for heat-sensitive traditional Chinese medicine.

Objective: Response surface analysis and regulating Donnan effect methodology were used to optimize the matrine concentration by nanofiltration techonology. Methods: On the basis of single factor experiment results, molecular weight cut-off (MWCO) of nanofiltration membrane, concentration and pH were selected as influencing factors to evaluate the retention rate of matrine and total alkaloids with Box-Behnken central composite experiment design, and then, the optimal concentration parameters were calculated in the conditions of pH 6-7 to regulate Donnan effect between alkaloids and nanofiltration membrane. Results: The retention rate of matrine was of positive relevance with the ethanol concentration. The optimal concentration parameters were as follows: cutting off molecular weight of 150, pH of 6.19, concentration of 204.3 μg/mL, ethanol concentration of 15%, the retention rate of matrine and total alkaloids were 94.41% and 97.63%, respectively. Conclusion: The combination of ethanol regulation Donnan effect and response surface analysis can well optimize the concentration process of S. flavescens extract by nanofiltration, and the results provide the references for nanofiltration concentration for heat-sensitive Chinese materia medicia.

Objective: To investigate the changing trends in the burden of cardiovascular diseases (CVD) in Zhejiang Province from 1990 to 2019, so as to provide insights into CVD control in the province. Methods: Based on the data of the Global Burden of Disease Study (GBD) 2019 (GBD 2019), the years lived with disability (YLD), years of life lost (YLL), disability-adjusted life years (DALY), YLD rate, YLL rate and DALY rate due to CVD were estimated to assess the burden of CVD in Zhejiang Province from 1990 to 2019. The changing trends in the burden of CVD were using annual percent change (APC) in Zhejiang Province from 1990 to 2019, and compared to China and global regions with different socio-demographic indexes (SDI). Results: The YLL rate (APC=-0.50%, F=22.366, P<0.001) and DALY rate due to CVD (APC=-0.20%, F=5.212, P=0.030) appeared a tendency towards a decline in Zhejiang Province from 1990 to 2019, while the YLD rate showed a tendency towards a rise (APC=1.92%, F=1 117.891, P<0.001). The YLL rate (APC=-1.09%, F=56.871, P<0.001), YLD rate (APC=1.92%, F=922.541, P<0.001) and DALY rate (APC=-0.60%, F=28.974, P<0.001) appeared the same tendency among women relative to among the whole populations, while only the YLD rate showed a clear-cut change among men, appearing a tendency towards a rise (APC=1.82%, F=1 238.423, P<0.001). Both the YLL rate and DALY rate appeared a tendency towards a decline among subjects at all age groups, with the most significant reduction among subjects at ages of 50 to 69 years (YLL rate: APC=-4.40%, F=1 443.608, P<0.001; DALY rate: APC=-3.82%, F=1 519.452, P<0.001). Among all types of CVD, the highest burden was measured in cerebrovascular diseases, with a standardized DALY rate of 1 359.7/105, and the most remarkable reduction in the standardized DALY rate was seen in rheumatic heart diseases. The burden of CVD in Zhejiang Province was lower than that in China and the majority of the world, with consistent changing trends with that in China and global regions with different SDI. Conclusions The overall burden of CVD appeared a tendency towards a decline in Zhejiang Province from 1990 to 2019, which was in agreement with that in China and global regions with different SDI. A remarkable reduction in the burden of CVD was seen among women, residents at ages of 50 to 69 years and cases with rheumatic heart diseases.

OBJECTIVE: To remove bacterial endotoxin from glycyrrhizic acid for injection by ultrasonic-assisted ultrafiltration technology. METHODS: On the basis of clarifying the influences of molecular weight cut off, ultrasonic power, glycyrrhizic acid concentration and pH,the ultrafiltration transmittance of glycyrrhizic acid and the rejection of bacterial endotoxin were selected as indexes to optimize the parameters for ultrasonic-assisted ultrafiltration. RESULTS: The impact of glycyrrhizic acid concentration was relatively low. The optimal separation conditions were as following: molecular weight cut off 10×103, ultrasonic power 300 W and pH 7.7. The predicted value of the ultrafiltration rejection of bacterial endotoxin was 93.7%, meanwhile the transmittance of glycyrrhizic acid was 92.2%, which was close to the model-predictive value. CONCLUSION: This mathematical model has good regression with high fitting degree, and can solve the separation contradiction between glycyrrhizic acid and bacterial endotoxin. This study provides scientific data for the purification of pharmaceutics in which saponins are the main components.